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Drug Interactions between letermovir and nirmatrelvir / ritonavir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

ritonavir letermovir

Applies to: nirmatrelvir / ritonavir and letermovir

GENERALLY AVOID: Coadministration with inducers of the P-glycoprotein (P-gp) efflux transporter and/or the uridine diphosphate glucuronosyltransferase (UGT) enzymes may decrease the plasma concentrations of letermovir according to the product labeling. Because letermovir is a substrate of P-gp and UGT 1A1 and 1A3, induction of the efflux transporter and metabolic enzymes may theoretically increase the clearance of letermovir. Concomitant use of rifampin initially resulted in a clinically insignificant increase in letermovir plasma concentrations (due to inhibition of organic anion transporting polypeptide [OATP] 1B1/3 and/or P-gp), followed by clinically significant decreases in letermovir plasma concentrations with continued rifampin coadministration (due to induction of P-gp/UGT).

MANAGEMENT: Due to the potential loss of efficacy, use of letermovir with inducers of the P-glycoprotein (P-gp) efflux transporter and/or the uridine diphosphate glucuronosyltransferase (UGT) enzymes is not recommended.

References (4)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Cerner Multum, Inc. (2015) "Canadian Product Information."
  4. (2017) "Product Information. Prevymis (letermovir)." Merck & Co., Inc

Drug and food interactions

Moderate

ritonavir food

Applies to: nirmatrelvir / ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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